title: Efficacy and safety of artemether-lumefantrine dispersible tablets compared with crushed commercial tablets in African infants and children with uncomplicated malaria: a randomised, single-blind, multicentre trial.
abstract: BACKGROUND
  Combination treatments, preferably containing an artemisinin derivative, are recommended to improve efficacy and prevent Plasmodium falciparum drug resistance. Our aim was to show non-inferiority of a new dispersible formulation of artemether-lumefantrine to the conventional crushed tablet in the treatment of young children with uncomplicated malaria.
  
  
  METHODS
  We did a randomised non-inferiority study on children weighing 5-35 kg with uncomplicated P falciparum malaria in Benin, Kenya, Mali, Mozambique, and Tanzania. The primary outcome measure was PCR-corrected 28-day parasitological cure rate. We aimed to show non-inferiority (with a margin of -5%) of dispersible versus crushed tablet. We constructed an asymptotic one-sided 97.5% CI on the difference in cure rates. A computer-generated randomisation list was kept centrally and investigators were unaware of the study medication administered. We used a modified intention-to-treat analysis. This trial is registered with ClinicalTrials.gov, number NCT00386763.
  
  
  RESULTS
  899 children aged 12 years or younger were randomly assigned to either dispersible (n=447) or crushed tablets (n=452). More than 85% of patients in each treatment group completed the study. 812 children qualified for the modified intention-to-treat analysis (n=403 vs n=409). The PCR-corrected day-28 cure rate was 97.8% (95% CI 96.3-99.2) in the group on dispersible formulation and 98.5% (97.4-99.7) in the group on crushed formulation. The lower bound of the one-sided 97.5% CI was -2.7%. The most common drug-related adverse event was vomiting (n=33 [7%] and n=42 [9%], respectively). No signs of ototoxicity or relevant cardiotoxicity were seen.
  
  
  CONCLUSIONS
  A six-dose regimen of artemether-lumefantrine with the new dispersible formulation is as efficacious as the currently used crushed tablet in infants and children, and has a similar safety profile.
authors.affiliation: Ifakara Health Institute, Dar es Salaam, Tanzania.
authors.forename: Salim
authors.initials: S
authors.lastname: Abdulla
authors.forename: Issaka
authors.initials: I
authors.lastname: Sagara
authors.forename: Steffen
authors.initials: S
authors.lastname: Borrmann
authors.forename: Umberto
authors.initials: U
authors.lastname: D'Alessandro
authors.forename: Raquel
authors.initials: R
authors.lastname: González
authors.forename: Mary
authors.initials: M
authors.lastname: Hamel
authors.forename: Bernhards
authors.initials: B
authors.lastname: Ogutu
authors.forename: Andreas
authors.initials: A
authors.lastname: Mårtensson
authors.forename: John
authors.initials: J
authors.lastname: Lyimo
authors.forename: Hamma
authors.initials: H
authors.lastname: Maiga
authors.forename: Philip
authors.initials: P
authors.lastname: Sasi
authors.forename: Alain
authors.initials: A
authors.lastname: Nahum
authors.forename: Quique
authors.initials: Q
authors.lastname: Bassat
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Juma
authors.forename: Lucas
authors.initials: L
authors.lastname: Otieno
authors.forename: Anders
authors.initials: A
authors.lastname: Björkman
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Beck
authors.forename: Kim
authors.initials: K
authors.lastname: Andriano
authors.forename: Marc
authors.initials: M
authors.lastname: Cousin
authors.forename: Gilbert
authors.initials: G
authors.lastname: Lefèvre
authors.forename: David
authors.initials: D
authors.lastname: Ubben
authors.forename: Zulfikarali
authors.initials: Z
authors.lastname: Premji
mesh_terms: D017954:Africa South of the Sahara; D000962:Antimalarials / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002626:Chemistry, Pharmaceutical; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D013607:Tablets; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D013607:Tablets